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The F atoms in the title compound, C19H17F2NO, attached to the meta positions of the two phenyl rings, are disordered with site occupancy factors of 0.5. The crystal is stabilized by strong inter­molecular N—H...O and van der Waals inter­actions.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807054165/om2176sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536807054165/om2176Isup2.hkl
Contains datablock I

CCDC reference: 672832

Key indicators

  • Single-crystal X-ray study
  • T = 298 K
  • Mean [sigma](C-C) = 0.003 Å
  • Disorder in main residue
  • R factor = 0.047
  • wR factor = 0.161
  • Data-to-parameter ratio = 12.0

checkCIF/PLATON results

No syntax errors found



Alert level C CELLV02_ALERT_1_C The supplied cell volume s.u. differs from that calculated from the cell parameter s.u.'s by > 2 Calculated cell volume su = 11.07 Cell volume su given = 9.00 PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent ..... ? PLAT301_ALERT_3_C Main Residue Disorder ......................... 8.00 Perc. PLAT366_ALERT_2_C Short? C(sp?)-C(sp?) Bond C9 - C10 ... 1.36 Ang. PLAT366_ALERT_2_C Short? C(sp?)-C(sp?) Bond C10 - C11 ... 1.38 Ang.
Alert level G PLAT793_ALERT_1_G Check the Absolute Configuration of C1 = ... S PLAT793_ALERT_1_G Check the Absolute Configuration of C2 = ... R PLAT793_ALERT_1_G Check the Absolute Configuration of C4 = ... S PLAT793_ALERT_1_G Check the Absolute Configuration of C5 = ... R
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 5 ALERT level C = Check and explain 4 ALERT level G = General alerts; check 6 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 2 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 0 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check

Comment top

Substituted piperidin-4-ones are important synthetic intermediates for the preparation of various alkaloids and pharmaceuticals (Ganellin & Spickett, 1965). Biological activities of the synthesized piperidin-4-one derivatives mainly depends on the substituents on the phenyl rings flanked either side of the secondary nitrogen. Only ortho fluoro substituted piperidin-4-one have been reported (Pham et al., 1998), which possess chair conformation.

The biological activities mainly depend on the stereochemistry (Buxton & Roberts, 1996) and the intramolecular and intermolecular hydrogen bonds with the fluorine atoms of the synthesized compound (Dunitz & Taylor, 1997; Evans & Seddon, 1997). In this study, we have incorporated the fluoro substituents at the one of the meta positions of the each phenyl groups on either side of the heterocyclic nitrogen to establish the stereochemistry and hydrogen bonding.

In the title compound C19H17F2 N O, the six membered heterocycle adopts a distorted chair conformation. The torsion angles deviate from the value of 56° expected for a perfect chair conformation (Kalsi, 1997). The equatorial dispositions of both methyl and phenyl rings which contain meta fluoro substitutents are identified by their torsion angles. The absolute configurations of the chiral atoms C1, C2, C4 and C5 are found to be R, S, R and S respectively.

According to the modified Mannich reaction reported by Noller & Baliah (1948), we expected to obtain 2,6-bis(3-fluorophenyl)piperidin-4-one by using 3-fluorobenzaldehyde, but the crystal structure reveals that the fluorine atoms occupy either side of the meta positions of each phenyl ring with a disordered site-occupancy factor of 0.5 (Fig.1).

In the crystal structure the molecules are inter linked through a strong N—H···O hydrogen bonding (Table 1, Fig.2), and also the molecules are held together by weak van der Waals interactions.

Related literature top

For related literature, see: Buxton & Roberts (1996); Dunitz & Taylor (1997); Evans & Seddon (1997); Ganellin & Spickett (1965); Kalsi (1997); Noller & Baliah (1948); Pham et al. (1998).

Experimental top

The title compound was prepared by the condensation of pentan-3-one, 3-flurobenzaldehyde and ammonium acetate in 1: 2: 1 molar ratio in ethanol as reported by Noller for the similar type of Mannich bases (Noller & Baliah, 1948). Diffraction quality crystal was obtained by recrystalization of the crude sample from ethanol.

Refinement top

The meta fluoro part of the molecule is disordered over two positions, the disorder refining to a 0.50:0.50 ratio. Nitrogen H atoms were located in a difference Fourier map and refined isotropically. Other hydrogen atoms were fixed geometrically and allowed to ride on the parent carbon atoms,with aromatic C—H = 0.93 Å, aliphatic C—H = 0.98 Å and methyl C—H = 0.96 Å. The displacement parameters were set for phenyl and aliphatic H atoms at Uiso(H) = 1.2Ueq(C) and for methyl H atoms at 1.5Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1] Fig. 1. ORTEP of the molecule with atoms represented as 50% probability ellipsoids. Hydrogen atoms are shown as atoms of arbitrary size.
[Figure 2] Fig. 2. Packing of molecules showing N—H···O interactions.
r-2,c-6-Bis(3-fluorophenyl)t-3,t-5-dimethylpiperidin-4-one top
Crystal data top
C19H17F2NOF(000) = 1312
Mr = 313.34Dx = 1.275 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 8210 reflections
a = 22.2891 (4) Åθ = 3.1–28.2°
b = 7.0516 (1) ŵ = 0.09 mm1
c = 23.4565 (4) ÅT = 298 K
β = 117.711 (2)°Block, colourless
V = 3263.89 (9) Å30.28 × 0.25 × 0.23 mm
Z = 8
Data collection top
Bruker APEXII CCD area-detector
diffractometer
2795 independent reflections
Radiation source: fine-focus sealed tube2337 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
ϕ and ω scansθmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
h = 2522
Tmin = 0.924, Tmax = 0.983k = 88
18121 measured reflectionsl = 2727
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.047Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.161H atoms treated by a mixture of independent and constrained refinement
S = 1.09 w = 1/[σ2(Fo2) + (0.0988P)2 + 1.2426P]
where P = (Fo2 + 2Fc2)/3
2795 reflections(Δ/σ)max < 0.001
232 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = 0.18 e Å3
Crystal data top
C19H17F2NOV = 3263.89 (9) Å3
Mr = 313.34Z = 8
Monoclinic, C2/cMo Kα radiation
a = 22.2891 (4) ŵ = 0.09 mm1
b = 7.0516 (1) ÅT = 298 K
c = 23.4565 (4) Å0.28 × 0.25 × 0.23 mm
β = 117.711 (2)°
Data collection top
Bruker APEXII CCD area-detector
diffractometer
2795 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 1999)
2337 reflections with I > 2σ(I)
Tmin = 0.924, Tmax = 0.983Rint = 0.024
18121 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0470 restraints
wR(F2) = 0.161H atoms treated by a mixture of independent and constrained refinement
S = 1.09Δρmax = 0.26 e Å3
2795 reflectionsΔρmin = 0.18 e Å3
232 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
C10.10456 (8)0.8562 (2)0.14454 (8)0.0382 (4)
H10.12580.86970.19150.046*
C20.09171 (8)1.0563 (2)0.11377 (9)0.0445 (4)
H20.07511.04040.06740.053*
C30.15962 (9)1.1548 (2)0.14083 (8)0.0443 (4)
C40.21485 (9)1.0504 (2)0.13318 (9)0.0467 (4)
H40.20191.04670.08710.056*
C50.21931 (8)0.8427 (2)0.15674 (8)0.0389 (4)
H50.23710.84300.20360.047*
C60.03966 (8)0.7444 (2)0.12237 (8)0.0411 (4)
C70.00105 (10)0.7053 (3)0.05773 (9)0.0555 (5)
H70.01220.74340.02730.067*
C80.06142 (10)0.6095 (3)0.03868 (11)0.0664 (6)
C90.08187 (10)0.5475 (3)0.08220 (11)0.0624 (6)
H90.12240.48210.06890.075*
C100.04097 (10)0.5845 (3)0.14551 (11)0.0616 (6)
C110.01918 (9)0.6832 (2)0.16639 (10)0.0503 (5)
H110.04570.70820.21000.060*
C120.26636 (9)0.7275 (2)0.14005 (9)0.0435 (4)
C130.33343 (9)0.6997 (3)0.18524 (11)0.0568 (5)
H130.34950.74720.22680.068*
C140.37635 (10)0.6011 (3)0.16827 (13)0.0693 (6)
C150.35459 (12)0.5283 (3)0.10790 (14)0.0726 (7)
H150.38410.46280.09710.087*
C160.28812 (13)0.5545 (3)0.06381 (12)0.0701 (6)
C170.24403 (10)0.6536 (3)0.07888 (10)0.0563 (5)
H170.19920.67080.04790.068*
C180.03924 (10)1.1699 (3)0.12326 (12)0.0623 (6)
H18A0.04951.16580.16780.093*
H18B0.00491.11670.09730.093*
H18C0.03991.29910.11070.093*
C190.28239 (12)1.1518 (3)0.16720 (15)0.0802 (8)
H19A0.27611.28420.15660.120*
H19B0.31341.09880.15360.120*
H19C0.30051.13650.21290.120*
F10.10284 (15)0.5924 (5)0.01925 (14)0.1008 (10)0.50
F1A0.06167 (13)0.5306 (4)0.18482 (13)0.0796 (8)0.50
F20.43768 (15)0.5665 (5)0.21028 (18)0.1115 (12)0.50
F2A0.26635 (16)0.4710 (4)0.00831 (14)0.0883 (9)0.50
N10.15164 (7)0.75695 (18)0.12719 (7)0.0406 (4)
O10.16979 (7)1.30766 (17)0.16775 (8)0.0638 (4)
H1A0.1522 (10)0.630 (3)0.1400 (9)0.060 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0348 (8)0.0340 (8)0.0452 (9)0.0019 (6)0.0181 (7)0.0023 (6)
C20.0432 (9)0.0339 (9)0.0553 (10)0.0061 (7)0.0219 (8)0.0053 (7)
C30.0528 (10)0.0281 (8)0.0564 (10)0.0026 (7)0.0291 (9)0.0060 (7)
C40.0503 (10)0.0349 (9)0.0655 (11)0.0019 (7)0.0358 (9)0.0023 (7)
C50.0355 (8)0.0350 (8)0.0476 (9)0.0001 (6)0.0204 (7)0.0024 (6)
C60.0345 (9)0.0326 (8)0.0544 (10)0.0042 (6)0.0191 (8)0.0007 (7)
C70.0506 (11)0.0536 (10)0.0556 (11)0.0062 (8)0.0189 (9)0.0021 (8)
C80.0451 (11)0.0588 (12)0.0700 (14)0.0056 (9)0.0055 (10)0.0035 (10)
C90.0373 (10)0.0522 (11)0.0937 (16)0.0067 (8)0.0271 (11)0.0111 (10)
C100.0477 (11)0.0570 (11)0.0918 (16)0.0066 (9)0.0423 (12)0.0098 (10)
C110.0445 (10)0.0498 (10)0.0611 (11)0.0037 (8)0.0284 (9)0.0058 (8)
C120.0409 (9)0.0336 (8)0.0615 (11)0.0008 (7)0.0284 (8)0.0052 (7)
C130.0420 (10)0.0563 (11)0.0719 (13)0.0046 (8)0.0265 (9)0.0074 (9)
C140.0443 (11)0.0614 (12)0.1080 (19)0.0127 (9)0.0404 (12)0.0151 (12)
C150.0716 (15)0.0526 (11)0.123 (2)0.0112 (10)0.0703 (15)0.0056 (12)
C160.0767 (15)0.0579 (12)0.0961 (17)0.0046 (10)0.0574 (14)0.0070 (11)
C170.0516 (11)0.0530 (10)0.0689 (13)0.0042 (8)0.0317 (10)0.0066 (9)
C180.0498 (11)0.0421 (10)0.0942 (15)0.0109 (8)0.0328 (11)0.0025 (9)
C190.0645 (14)0.0447 (11)0.150 (2)0.0121 (9)0.0655 (15)0.0101 (12)
F10.089 (2)0.109 (2)0.0782 (19)0.0390 (18)0.0159 (16)0.0186 (16)
F1A0.0718 (16)0.105 (2)0.0896 (17)0.0439 (14)0.0609 (14)0.0249 (15)
F20.0576 (18)0.140 (3)0.132 (3)0.0327 (18)0.0401 (18)0.013 (2)
F2A0.110 (2)0.0906 (19)0.0861 (18)0.0161 (16)0.0635 (17)0.0242 (15)
N10.0372 (8)0.0291 (7)0.0569 (9)0.0016 (5)0.0231 (7)0.0009 (6)
O10.0676 (9)0.0369 (7)0.0964 (11)0.0052 (6)0.0462 (8)0.0112 (7)
Geometric parameters (Å, º) top
C1—N11.468 (2)C9—H90.9300
C1—C61.511 (2)C10—F1A1.266 (3)
C1—C21.550 (2)C10—C111.382 (3)
C1—H10.9800C11—H110.9300
C2—C31.511 (2)C12—C171.384 (3)
C2—C181.517 (2)C12—C131.387 (3)
C2—H20.9800C13—C141.383 (3)
C3—O11.216 (2)C13—H130.9300
C3—C41.515 (2)C14—F21.283 (4)
C4—C191.515 (3)C14—C151.366 (4)
C4—C51.552 (2)C15—C161.369 (3)
C4—H40.9800C15—H150.9300
C5—N11.466 (2)C16—F2A1.300 (3)
C5—C121.515 (2)C16—C171.379 (3)
C5—H50.9800C17—H170.9300
C6—C111.378 (3)C18—H18A0.9600
C6—C71.385 (3)C18—H18B0.9600
C7—C81.381 (3)C18—H18C0.9600
C7—H70.9300C19—H19A0.9600
C8—F11.244 (3)C19—H19B0.9600
C8—C91.369 (3)C19—H19C0.9600
C9—C101.359 (3)N1—H1A0.95 (2)
N1—C1—C6110.45 (13)F1A—C10—C9116.8 (2)
N1—C1—C2107.83 (13)F1A—C10—C11121.0 (2)
C6—C1—C2112.00 (13)C9—C10—C11122.1 (2)
N1—C1—H1108.8C6—C11—C10119.79 (19)
C6—C1—H1108.8C6—C11—H11120.1
C2—C1—H1108.8C10—C11—H11120.1
C3—C2—C18112.69 (14)C17—C12—C13118.64 (17)
C3—C2—C1106.91 (13)C17—C12—C5120.78 (16)
C18—C2—C1113.61 (15)C13—C12—C5120.54 (17)
C3—C2—H2107.8C14—C13—C12119.7 (2)
C18—C2—H2107.8C14—C13—H13120.2
C1—C2—H2107.8C12—C13—H13120.2
O1—C3—C2122.27 (15)F2—C14—C15117.5 (3)
O1—C3—C4121.79 (16)F2—C14—C13120.5 (3)
C2—C3—C4115.93 (14)C15—C14—C13121.9 (2)
C3—C4—C19111.81 (15)C14—C15—C16118.05 (19)
C3—C4—C5109.72 (13)C14—C15—H15121.0
C19—C4—C5111.96 (16)C16—C15—H15121.0
C3—C4—H4107.7F2A—C16—C15117.7 (2)
C19—C4—H4107.7F2A—C16—C17120.5 (2)
C5—C4—H4107.7C15—C16—C17121.6 (2)
N1—C5—C12109.89 (13)C16—C17—C12120.1 (2)
N1—C5—C4109.85 (13)C16—C17—H17120.0
C12—C5—C4110.57 (13)C12—C17—H17120.0
N1—C5—H5108.8C2—C18—H18A109.5
C12—C5—H5108.8C2—C18—H18B109.5
C4—C5—H5108.8H18A—C18—H18B109.5
C11—C6—C7118.76 (16)C2—C18—H18C109.5
C11—C6—C1120.20 (15)H18A—C18—H18C109.5
C7—C6—C1121.02 (16)H18B—C18—H18C109.5
C8—C7—C6119.69 (19)C4—C19—H19A109.5
C8—C7—H7120.2C4—C19—H19B109.5
C6—C7—H7120.2H19A—C19—H19B109.5
F1—C8—C9116.6 (2)C4—C19—H19C109.5
F1—C8—C7121.2 (3)H19A—C19—H19C109.5
C9—C8—C7121.8 (2)H19B—C19—H19C109.5
C10—C9—C8117.82 (18)C5—N1—C1112.54 (12)
C10—C9—H9121.1C5—N1—H1A112.6 (12)
C8—C9—H9121.1C1—N1—H1A105.6 (12)
N1—C1—C2—C359.72 (17)C8—C9—C10—F1A178.1 (2)
C6—C1—C2—C3178.56 (14)C8—C9—C10—C110.7 (3)
N1—C1—C2—C18175.32 (15)C7—C6—C11—C100.1 (3)
C6—C1—C2—C1853.6 (2)C1—C6—C11—C10178.65 (15)
C18—C2—C3—O10.8 (2)F1A—C10—C11—C6178.4 (2)
C1—C2—C3—O1124.69 (18)C9—C10—C11—C61.1 (3)
C18—C2—C3—C4179.93 (15)N1—C5—C12—C1740.4 (2)
C1—C2—C3—C454.55 (19)C4—C5—C12—C1781.0 (2)
O1—C3—C4—C194.6 (3)N1—C5—C12—C13141.82 (16)
C2—C3—C4—C19174.68 (17)C4—C5—C12—C1396.75 (19)
O1—C3—C4—C5129.41 (17)C17—C12—C13—C140.5 (3)
C2—C3—C4—C549.8 (2)C5—C12—C13—C14177.24 (17)
C3—C4—C5—N149.75 (19)C12—C13—C14—F2176.8 (3)
C19—C4—C5—N1174.51 (16)C12—C13—C14—C150.4 (3)
C3—C4—C5—C12171.21 (14)F2—C14—C15—C16176.1 (3)
C19—C4—C5—C1264.0 (2)C13—C14—C15—C160.4 (3)
N1—C1—C6—C11120.53 (16)C14—C15—C16—F2A174.2 (2)
C2—C1—C6—C11119.27 (16)C14—C15—C16—C170.9 (3)
N1—C1—C6—C761.0 (2)F2A—C16—C17—C12174.2 (2)
C2—C1—C6—C759.2 (2)C15—C16—C17—C120.8 (3)
C11—C6—C7—C81.1 (3)C13—C12—C17—C160.0 (3)
C1—C6—C7—C8177.39 (16)C5—C12—C17—C16177.81 (17)
C6—C7—C8—F1171.2 (3)C12—C5—N1—C1176.82 (12)
C6—C7—C8—C91.5 (3)C4—C5—N1—C161.31 (17)
F1—C8—C9—C10172.4 (3)C6—C1—N1—C5170.52 (13)
C7—C8—C9—C100.6 (3)C2—C1—N1—C566.81 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.95 (2)2.34 (2)3.2785 (18)169.7 (16)
Symmetry code: (i) x, y1, z.

Experimental details

Crystal data
Chemical formulaC19H17F2NO
Mr313.34
Crystal system, space groupMonoclinic, C2/c
Temperature (K)298
a, b, c (Å)22.2891 (4), 7.0516 (1), 23.4565 (4)
β (°) 117.711 (2)
V3)3263.89 (9)
Z8
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.28 × 0.25 × 0.23
Data collection
DiffractometerBruker APEXII CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 1999)
Tmin, Tmax0.924, 0.983
No. of measured, independent and
observed [I > 2σ(I)] reflections
18121, 2795, 2337
Rint0.024
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.047, 0.161, 1.09
No. of reflections2795
No. of parameters232
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.26, 0.18

Computer programs: APEX2 (Bruker, 2004), SAINT (Bruker, 2004), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.95 (2)2.34 (2)3.2785 (18)169.7 (16)
Symmetry code: (i) x, y1, z.
 

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